ArticleAmerican journal of human genetics2021
Unique variants in CLCN3, encoding an endosomal anion/proton exchanger, underlie a spectrum of neurodevelopmental disorders.
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Article in American journal of human genetics, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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28citing papers in PubMed
2.4field-weighted citation impact, top 10% of its field
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Who cites it
28 citing papers in PubMed, 44 citations in OpenAlex.
- Pathogenic O-GlcNAc dyshomeostasis is associated with cortical malformations and hyperactivity.eLife · 2026Article
- Abnormal ClC-3/TMEM9-mediated endosomal ion transport in CLCN3-associated neurodevelopmental disease.EMBO molecular medicine · 2026Article
- Dominant Action ofCells · 2025Article
- Endosomal 2Cl-/H+ exchangers regulate neuronal excitability by tuning Kv7/KCNQ channel density.Brain : a journal of neurology · 2025Article
- Structural basis of ClC-3 transporter inhibition by TMEM9 and PtdIns(3,5)PNature structural & molecular biology · 2025Article
- Disruption of ClC-3-mediated 2ClScientific reports · 2025Article
- Long-read sequencing reveals the RNA isoform repertoire of neuropsychiatric risk genes in human brain.Genome biology · 2025Article
- Article
- Endosomal chloride/proton exchangers need inhibitory TMEM9 β-subunits for regulation and prevention of disease-causing overactivity.Nature communications · 2025Article
- ALLIN: A tool for annotation of a protein alignment combined with structural visualization.The Journal of general physiology · 2025Article
- A Unique Derivative Chromosome 4 with a Predominant 4p16.3 Microduplication Phenotype and a Literature Review.Molecular syndromology · 2025Article
- Human stem cell-based models to study synaptic dysfunction and cognition in schizophrenia: A narrative review.Schizophrenia research · 2024Review
- Article
- TMEM9B Regulates Endosomal ClC-3 and ClC-4 Transporters.Life (Basel, Switzerland) · 2024Article
- Structural basis of adenine nucleotides regulation and neurodegenerative pathology in ClC-3 exchanger.Nature communications · 2024Article
- Expanding the genetic and phenotypic relevance of CLCN4 variants in neurodevelopmental condition: 13 new patients.Journal of neurology · 2024Article
- Chloride/proton antiporters ClC3 and ClC5 support bone formation in mice.Bone reports · 2024Article
- Article
- Distinct mouse models of Stargardt disease display differences in pharmacological targeting of ceramides and inflammatory responses.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- CryoEM structures of the human CLC-2 voltage gated chloride channel reveal a ball and chain gating mechanism.bioRxiv : the preprint server for biology · 2023Article
Corrections and comments
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Authors and funding
40 authors at 16 institutions in 6 countries.
Anna R DuncanDivision of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA.
Maya M PolovitskayaLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; Max-Delbrück-Centrum für Molekulare Medizin (MDC), 13125 Berlin, Germany.
Héctor Gaitán-PeñasUnitat de Fisiologia, Departament de Ciències Fisiològiques, IDIBELL-Institute of Neurosciences, Universitat de Barcelona-CIBERER, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Sara BertelliIstituto di Biofisica, 16149 Genova, Italy; Scuola Internazionale Superiore di Studi Avanzati (SISSA), 34136 Trieste, Italy.
Grace E VanNoyCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA.
Patricia E GrantDivision of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; Department of Radiology, Boston Children's Hospital, Boston, MA 02115, USA.
Anne O'Donnell-LuriaCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Division of Genetics & Genomics, Department of Pediatrics, Boston Children's Hospital, MA 02115, USA; Analytic and Translational Genomics Unit, Massachusetts General Hospital, Boston, MA 02114, USA.
Zaheer ValivullahCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alysia Kern LovgrenCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Elaina M EnglandCenter for Mendelian Genomics, Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Division of Genetics & Genomics, Department of Pediatrics, Boston Children's Hospital, MA 02115, USA.
Emanuele AgoliniTranslational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Jill A MaddenThe Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Division of Genetics & Genomics, Department of Pediatrics, Boston Children's Hospital, MA 02115, USA.
Klaus Schmitz-AbeDivision of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA.
Amy KritzerDivision of Genetics & Genomics, Department of Pediatrics, Boston Children's Hospital, MA 02115, USA.
Pamela HawleyDivision of Genetics & Genomics, Department of Pediatrics, Boston Children's Hospital, MA 02115, USA.
Antonio NovelliTranslational Cytogenomics Research Unit, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Paolo AlfieriChild and Adolescent Neuropsychiatry Unit, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy.
Giovanna Stefania ColafatiOncological Neuroradiology Unit, Bambino Gesù Children's Hospital, IRCCS, 00146 Rome, Italy.
Dagmar WieczorekInstitute of Human Genetics, Medical Faculty, Heinrich-Heine University, 40225 Düsseldorf, Germany.
Konrad PlatzerInstitute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany.
Johannes LuppeInstitute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany.
Margarete Koch-HogrebeVestische Kinder-und Jugendklinik Datteln, Universität Witten-Herdecke, 45711 Datteln, Germany.
Rami Abou JamraInstitute of Human Genetics, University of Leipzig Medical Center, 04103 Leipzig, Germany.
Juanita Neira-FresnedaDepartment of Human Genetics, Emory University School of Medicine, Atlanta, GA 30322, USA.
Anna LehmanProvincial Medical Genetics Program, University of British Columbia, Department of Medical Genetics, Children's and Women's Health Center of British Columbia, Vancouver, BC V6H 3N1, Canada.
Cornelius F BoerkoelProvincial Medical Genetics Program, University of British Columbia, Department of Medical Genetics, Children's and Women's Health Center of British Columbia, Vancouver, BC V6H 3N1, Canada.
Kimberly SeathProvincial Medical Genetics Program, University of British Columbia, Department of Medical Genetics, Children's and Women's Health Center of British Columbia, Vancouver, BC V6H 3N1, Canada.
Lorne ClarkeProvincial Medical Genetics Program, University of British Columbia, Department of Medical Genetics, Children's and Women's Health Center of British Columbia, Vancouver, BC V6H 3N1, Canada.
CAUSES StudyProvincial Medical Genetics Program, University of British Columbia, Department of Medical Genetics, Children's and Women's Health Center of British Columbia, Vancouver, BC V6H 3N1, Canada.
Yvette van IerlandErasmus University Medical Center, Department of Clinical Genetics, 3000 CA Rotterdam, the Netherlands.
Emanuela ArgilliBrain Development Research Program, Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Elliott H SherrBrain Development Research Program, Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
Andrea MaioranaNeonatology, Ospedale San Giovanni Calibita Fatebenefratelli, 00186 Roma, Italy.
Thilo DielDivision of Neonatology and Pediatric Critical Care Medicine, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Maja HempelInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Tatjana BierhalsInstitute of Human Genetics, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Raúl EstévezUnitat de Fisiologia, Departament de Ciències Fisiològiques, IDIBELL-Institute of Neurosciences, Universitat de Barcelona-CIBERER, L'Hospitalet de Llobregat, 08907 Barcelona, Spain.
Thomas J JentschLeibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), 13125 Berlin, Germany; Max-Delbrück-Centrum für Molekulare Medizin (MDC), 13125 Berlin, Germany; NeuroCure Cluster of Excellence, Charité Universitätsmedizin Berlin, 10117 Berlin, Germany. Electronic address: jentsch@fmp-berlin.de.
Michael PuschIstituto di Biofisica, 16149 Genova, Italy.
Pankaj B AgrawalDivision of Newborn Medicine, Department of Pediatrics, Boston Children's Hospital, Boston, MA 02115, USA; The Manton Center for Orphan Disease Research, Boston Children's Hospital, Boston, MA 02115, USA; Division of Genetics & Genomics, Department of Pediatrics, Boston Children's Hospital, MA 02115, USA. Electronic address: pagrawal@enders.tch.harvard.edu.
Boston Children's Hospital · USBroad Institute · USBambino Gesù Children's Hospital · ITUniversity of British Columbia · CALeipzig University · DEUniversität Hamburg · DEInstitut d'Investigació Biomédica de Bellvitge · ESMax Delbrück Center · DEUniversity of California, San Francisco · USEmory University · USErasmus MC · NLFatebenefratelli Hospital · ITHeinrich Heine University Düsseldorf · DEInstituto di Biofisica · ESScuola Internazionale Superiore di Studi Avanzati · ITWitten/Herdecke University · DE
Funding
Toward better characterization and clinical trial readiness for targeting neuropsychiatric manifestations in PTEN pathogenic variantsU54NS092090 · NINDS · BOSTON CHILDREN'S HOSPITAL · PI M. Pilar Trelles · 2014 to 2026
$20.1MJoint Center for Mendelian GenomicsUM1HG008900 · NHGRI · BROAD INSTITUTE, INC. · PI O'DONNELL-LURIA, ANNE, REHM, HEIDI L · 2016 to 2020
$16.5MDe novo copy number variation and gene discovery in human brain malformationsR01NS058721 · NINDS · UNIVERSITY OF CHICAGO · PI ARGILLI, EMANUELA · 2008 to 2025
$10.9MGenetic Analysis and Manipulation Core (GAEC)P50HD105351 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Hisashi Umemori · 2021 to 2026
$9.4MMouse Neurodevelopmental Behavior CoreU54HD090255 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI POMEROY, SCOTT LOREN · 2016 to 2020
$5.2MNeonatal Research Training ProgramT32HD098061 · NICHD · BOSTON CHILDREN'S HOSPITAL · PI Stella Kourembanas, Martha C. Sola-Visner · 2019 to 2026
$4.0MA powerful web-based discovery platform for rare disease geneticsR01HG009141 · NHGRI · BROAD INSTITUTE, INC. · PI QUINLAN, AARON R, REHM, HEIDI L · 2017 to 2020
$2.9MSPEG is Critical in Skeletal Muscle Development and FunctionR01AR068429 · NIAMS · BOSTON CHILDREN'S HOSPITAL · PI AGRAWAL, PANKAJ B · 2015 to 2019
$1.9MNHGRI NIH HHS R01 HG009141NHGRI NIH HHS UM1 HG008900NIAMS NIH HHS R01 AR068429NICHD NIH HHS P50 HD105351NICHD NIH HHS T32 HD098061NICHD NIH HHS U54 HD090255NINDS NIH HHS R01 NS058721NINDS NIH HHS U54 NS092090
Abstract
The genetic causes of global developmental delay (GDD) and intellectual disability (ID) are diverse and include variants in numerous ion channels and transporters. Loss-of-function variants in all five endosomal/lysosomal members of the CLC family of Cl
Indexed as
Disease Models, AnimalMutationPhenotypeAdolescentAnimalsChildChild, PreschoolChloride ChannelsFemaleHomozygoteHumansInfantInfant, NewbornIon ChannelsMaleMiceChloride ChannelsClC-3 channelIon ChannelsacidificationCLCNgain of functionhippocampusintellectual disabilityneurodevelopmental delaypH sensitivityvoltage gated chloride channel
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